Abstract
Joint pain is the main complaint in patients affected by osteoarthritis (OA), and NSAIDs are commonly used to treat pain associated with OA. Over the past few years, cyclo-oxygenase (COX)-2-selective inhibitors have been proved to have certain advantages over non-selective NSAIDs and have been increasingly used for pain management in patients with OA.
Objective:The main objective of this randomised, double-blind, within-patient study was to compare the analgesic efficacy of three COX-2 inhibitors in 30 patients affected by symptomatic OA of the knee. We evaluated the effects of oral nimesulide (100mg), celecoxib (200mg) and rofecoxib (25mg). Each drug was administered for 7 days.
Methods: Analgesic efficacy was determined using the patient's assessment of pain on a visual analogue scale (VAS) and by total pain relief over 3 hours (TOPAR3) on the first and last days of treatment. In addition, the overall analgesic efficacy and tolerability were determined by a global assessment by the patient at the end of each week of treatment, using 5-point categorical scales. At the end of the study, each patient was asked about which of the three forms of treatment they would choose as a continuation of the pain therapy.
Results: Taking all the results into consideration, nimesulide proved to be significantly more effective in providing symptomatic relief than did celecoxib and rofecoxib. Furthermore, nimesulide provided more rapid relief of pain associated with walking than did the other two drugs tested. Patients expressed similar preference for nimesulide and rofecoxib, but a lesser preference for celecoxib treatment. No patient withdrew from the study because of adverse events and the three different forms of treatment were generally safe and well tolerated.
Conclusion: The present data confirm our previous observations in patients with rheumatoid arthritis, further suggesting that nimesulide represents an effective agent for the treatment of joint pain, with particular reference to the rapid onset of its analgesic effect.
Similar content being viewed by others
References
American College of Rheumatology subcommittee on osteoarthritis guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee. Arthritis Rheum 2000; 43: 1905–15
Pincus T, Swearingen C, Cummins P, et al. Preference for nonsteroidal antiinflammatory drugs versus acetaminophen and concomitant use of both types of drugs in patients with osteoarthritis. J Rheumatol 2000; 27: 1020–7
Wolfe F, Zhao S, Lao S. Preference for non-steroidal-anti-inflammatory drugs over acetaminophen by rheumatic disease patients: a survey of 1799 patients with osteoarthritis, rheumatoid arthritis and fibromyalgia. Arthritis Rheum 2000; 43: 378
Altman RD,IAP Study Group. Ibuprofen, acetaminophen and placebo in osteoarthritis of the knee: a six-day double-blind study. Arthritis Rheum 1999; 42 Suppl. 9: S403
Geba GP, Weaver AL, Polis AB, et al. Efficacy of rofecoxib, celecoxib, and acetaminophen in osteoarthritis of the knee. JAMA 2002; 287: 64–71
Baba H, Kohno T, Moore KA, et al. Direct activation of rat spinal dorsal horn neurons by prostaglandin E 2. J Neurosci 2001; 21: 1750–6
Samad TA, Moore KA, Sapirstein A, et al. Interleukin-1β-mediated induction of COX-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature 2001; 410: 471–5
Woolf CJ, Salter MW Neuronal plasticity: increasing the gain in pain. Science 2000; 288: 1765–8
Turnbach ME, Seth Spraggins D, Randich A. Spinal administration of prostaglandin E2 or prostaglandin F2α primarly produces mechanical hyperalgesia that is mediated by nociceptive specific spinal dorsal horn neurons. Pain 2002; 97: 33–45
Hawkey C, Laine L, Simon T, et al. Comparison of the effect of rofecoxib (a cyclooxygenase-2 inhibitor), ibuprofen, and placebo on the gastroduodenal mucosa of patients with osteoarthritis: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2000; 43: 370–7
Hawkey CJ, Skelly MM. Gastrointestinal safety of COX-2 inhibitors. Curr Pharm Des 2002; 8: 1077–89
Clemett D, Goa KL. Celecoxib: a review of its use in osteoarthritis, rheumatoid arthritis, and acute pain. Drugs 2000; 59: 957–80
Matheson AJ, Figgitt DP. Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis. Drugs 2001; 61: 833–65
Warner TD, Giuliano F, Vojnovic I, et al. Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc Natl Acad Sci USA 1999; 96: 7563–8
Cryer B, Feldman M. Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med 1998; 104: 413–21
Patrono C, Patrignani P, Garcia Rodriguez LA. Cyclooxygenase-selective inhibition of prostanoid formation: transducing biochemical selectivity into clinical readouts. J Clin Invest 2001; 108: 7–13
Bennett A. Nimesulide: a well-established cyclooxygenase-2 inhibitor with many other pharmacological properties relevant to inflammatory diseases. In: Vane JR, Botting RM, editors. Therapeutic roles of selective COX-2 inhibitors. London: William Harwey Press, 2001: 524–40
Dreiser RL, Riebenfeld D. Nimesulide in the treatment of osteoarthritis. Double-blind studies in comparison with piroxicam, ketoprofen or placebo. Drugs 1993; 45 Suppl. 1: 191–5
Locker PW, Pawlowsky C, Friedrich I, et al. Double-blind, randomised, multicentre clinical study evaluating the efficacy and tolerability of nimesulide in comparison with etodolac in patients suffering from osteoarthritis of the knee. Eur J Rheumatol Inflamm 1994; 14: 29–38
Porto A, Reis C, Perdigoto R, et al. Gastroduodenal tolerability of nimesulide and diclofenac in patients with osteoarthritis. Curr Ther Res 1998; 59: 654–65
Huskisson EC, Macciocchi A, Rahlfs VW, et al. Nimesulide versus diclofenac in the treatment of osteoarthritis of the hip or knee: an active controlled equivalence study. Curr Ther Res 1999; 60: 253–65
Bianchi M, Broggini M. Anti-hyperalgesic effects of nimesulide: studies in rats and humans. Int J Clin Practice 2002; Suppl. 128: 11–9
Altman RD. Criteria for the classification of osteoarthritis of the knee and hip. Scand J Rheumatol Suppl 1987; 65: 31–9
Young MK, Bresnitz EA, Strom BL. Sample size nomograms for interpreting negative clinical results. Ann Int Med 1983; 99: 248–51
Collins SL, Moore A, McQuay HJ. The visual analogue scale: what is moderate pain in millimetres? Pain 1997; 72: 95–7
Odding E, Valkenburg HA, Algra D, et al. Associations of radiological osteoarthritis of the hip and knee with locomotor disability in the Rotterdam Study. Ann Rheum Dis 1998; 57: 203–8
Urwin M, Symmons D, Allison T, et al. Estimating the burden of musculoskeletal disorders in the community: the comparative prevalence of symptoms at different anatomical sites, and the relation to social deprivation. Ann Rheum Dis 1998; 57: 649–55
Felson DT, Lawrence RC, Dieppe PA, et al. Osteoarthritis: new insights. Ann Intern Med 2000; 133: 726–37
Links C, Jordan K, Croft P. Measuring the population impact of the knee pain and disability with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Pain 2002; 100: 55–64
Day R, Morrison B, Luza A, et al. A randomised trial of the efficacy and tolerability of the COX-2 inhibitor rofecoxib vs ibuprofen in patients with osteoarthritis. Rofecoxib/ Ibuprofen Comparator Study Group. Arch Intern Med 2000; 160: 1781–7
Bensen WG, Fiechtner JJ, McMillen J, et al. Treatment of osteoarthritis with celecoxib, a cyclooxygenase-2 inhibitor: a randomized controlled trial. Mayo Clin Proc 1999; 74: 1095–105
Williams GW, Hubbard RC, Yu SS, et al. Comparison of once-daily and twice-daily administration of celecoxib for the treatment of osteoarthritis of the knee. Clin Ther 2001; 2: 213–27
Vane JR, Warner TD. Nomenclature for COX-2 inhibitors. Lancet 2000; 356: 1373–4
Seibert K, Zhang Y, Leahy K, et al. Pharmacological and biochemical demonstration of the role of cyclooxygenase-2 in inflammation and pain. Proc Natl Acad Sci 1994; 91: 12013–7
Willingale HL, Gardiner NJ, Mclymont N, et al. Prostanoids synthesized by cyclo-oxygenase isoforms in rat spinal cord and their contribution to the development of neuronal hyperexcitability. Br J Pharmacol 1997; 122: 1593–604
Hinz B, Brune K. Cyclooxygenase-2 —10 years later. J Pharmacol Exp Ther 2002; 300: 367–75
Tonussi CR, Ferreira SH. Mechanism of diclofenac analgesia: direct blockade of inflammatory sensitization. Eur J Pharmacol 1994; 251: 173–9
Ballou LR, Botting RM, Goorha S, et al. Nociception in cyclooxygenase isoenzyme-deficient mice. Proc Natl Acad Sci USA 2000; 97: 10272–6
Steinmeyer J. Pharmacological basis for the therapy of pain and inflammation with nonsteroidal anti-inflammatory drugs. Arthritis Res 2000; 2: 379–85
Voilley N, de Weille J, Mamet J, et al. Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. J Neurosci 2001; 21: 8026–33
Jain NK, Patil CS, Kulkarni SK, et al. Participation of the nitric oxide-cGMP pathway in the peripheral antinociceptive effect of nimesulide. Analgesia 2002; 6: 27–37
Chandrasekharan NV, Dai H, Lamar Turepu Roos K, et al. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci USA 2002; 99: 13926–31
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bianchi, M., Broggini, M. A Randomised, Double-Blind, Clinical Trial Comparing the Efficacy of Nimesulide, Celecoxib and Rofecoxib in Osteoarthritis of the Knee. Drugs 63 (Suppl 1), 37–46 (2003). https://doi.org/10.2165/00003495-200363001-00006
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-200363001-00006